Effects of intrathecally administered lamotrigine, a glutamate release inhibitor, on short- and long-term models of hyperalgesia in rats.
BACKGROUND
Lamotrigine is a sodium channel blocker that inhibits the neuronal release of glutamate. Systemic administration of lamotrigine induces analgesia in short- and long-term models of hyperalgesia in rats. Considering the key role of N-methyl-D-aspartate receptors in the sensitization of dorsal horn neurons that leads to hyperalgesia, the author hypothesizes that intrathecally injected lamotrigine would be effective in reducing the hyperalgesia.


METHODS
Short-term hyperalgesia was induced by unilateral intraplantar injection of prostaglandin E2. Long-term hyperalgesia was produced by treating rats with streptozotocin, which causes diabetic neuropathy and, in a different group of animals, by loose ligation of the sciatic nerve (chronic constriction injury). Hyperalgesia was assessed by measuring withdrawal reaction time after paw pressure, and analgesia was measured by the thermal tail-flick test.


RESULTS
In the short-term model, intrathecally administered lamotrigine (12.5, 25.0, and 100.0 microg) produced a dose-dependent increase in the reaction time of the hyperalgesic paw. The highest dose that completely restored the reaction time to control levels (26-29 s) from the hyperalgesic levels (12-15 s) did not affect the reaction time of the normal contralateral paw. In the tail-flick test, a consistent effect could be observed only with doses of 200 microg, which caused transient motor impairment of the hind paws. In the long-term models of hyperalgesia, intrathecally administered lamotrigine produced a dose-dependent and long-lasting (24-48 h) antihyperalgesic effect.


CONCLUSIONS
Intrathecally administered lamotrigine produced a spinal, dose-dependent, and long-lasting antihyperalgesic effect in short- and long-term neuropathic models of hyperalgesia.
Klamt
J G
JG
Department of Surgery, Orthopedics, and Traumatology, Faculty of Medicine of Ribeirão Preto-USP, Brazil. jgklamt@fmrp.usp.br
D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D003929:Diabetic Neuropathies / Q000139:chemically induced; D015232:Dinoprostone; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D007278:Injections, Spinal; D000077213:Lamotrigine; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D026941:Sodium Channel Blockers; D013311:Streptozocin; D014227:Triazines / Q000494:pharmacology / Q000627:therapeutic use*
D000700:Analgesics; D026941:Sodium Channel Blockers; D014227:Triazines; D013311:Streptozocin; D015232:Dinoprostone; D000077213:Lamotrigine